DESCRIPTION (Adapted from the application): The objective of the candidate's research is a thorough biophysical and structural characterization of the functional domains off the two subunits of core binding factor (CBF) as well as the relevant complexes involved. We are employing NMR spectroscopy for the structure determinations of CBF beta (1-141) as well as a Runt domain-DNA complex and propose to extend these studies to the ternary complex. Assignment of the proteins and DNA as well as collection of NOESY and J-coupling data will employ heteronuclear multi-dimensional NMR methodology. The long-term aim of this work is structure determinations as well as biophysical studies of relevant domains of the oncoproteins associated with CBF. a. Candidate: Dr. John H. Bushweller is an assistant professor in the Department of Chemistry at Dartmouth College. Since 1991 he has authored or co-authored articles in several journals including Biochemistry, J. Biol. Chem., J. Mol. Biol., and Cell. He is the recipient of three grants including an NIH First award in 1996. b. Career Development Plan: The candidate plans to develop a high caliber structural biology research group at Dartmouth. He also plans to broaden his knowledge by participating in the Faculty Research Club of the Department of Biochemistry. c. Research Plan: The objective of the proposed research is to do a biophysical and structural characterization of the functional domains of the two subunits of core binding factor (CBF), as well as, the relevant complexes involved. d. Environment and Institutional Commitment: Dartmouth College has provided the candidate with good laboratory space, computer support and, most of the available time on the institution's NMR spectrometer. In addition, three graduate student stipends are provided by the Department of Chemistry.